Sodium valproate induced Steven-Johnson syndrome (SJS). The antiepileptics phenytoin, carbamazepine, phenobarbitone, and
Primidone can cause hypersensitivity reactions. It is rarely reported by sodium valproate.
1 The common side effects of
Sodium Valproate include anorexia, nausea, vomiting, sedation, ataxia, tremor, alopecia, stimulation of appetite, elevation of hepatic transaminases, and rarely fulminant hepatitis.
2 In a study done on 245 people admitted with Toxic Epidermal Necrolysis (TEN) or SJS and 1147 people admitted for other reasons, drugs used before the onset of symptoms was studied and the crude relative risk for SJS or TEN was found to be as follows: carbamazepine 90,
Phenytoin 53,
Phenobarbitone 45 and
Sodium Valproate 25.
3
SJS is a type IV hypersensitivity reaction in which a drug or its metabolite initiates autoimmune reactions by stimulating cytotoxic T cells and T helper cells.
4 Valproic acid is known to inhibit mitochondrial respiration resulting in mitochondrial dysfunction, oxidative stress, and increased cell death. Microvesicular hepatosteatosis is a peculiar feature of valparin induced hepatitis and is suggestive of mitochondrial involvement especially the ß-oxidation.
5
The clinical features of SJS include fever, sigs of upper respiratory tract involvement and initially conjunctivitis later on followed by the detachment of mucous membranes (oropharyngeal, conjunctival, anogenital and nasal). There is involvement of more than one mucous membrane. Cutaneous lesions may be in form in the form of dusky erythematous macules, purpura or target lesions associated with pain and burning sensation. The cutaneous involvement is symmetrical and involves trunk and limbs over 2–3 days. Also, there blister formation and shear pressure over the skin may lead to epidermal detachment also known as pseudo-Nikolsky's sign.
6
The management of SJS involves multidisciplinary approach. Prompt withdrawal of the inciting agent, early initiation of oral or parenteral corticosteroids
Prednisolone 1-2 mg/kg/day for 7-10 days, and providing other supportive measures as topical pain anesthetics, antiseptics, eye care to prevent scar form the basis of treatment and prevention of complications.
Intravenous Immunoglobulin has some role in amelioration of symptoms in SJS however not much role has been established.
6| References : |
- Kumar PN, Kumar SK. Stevens-Johnson syndrome induced by Sodium Valproate. Indian J Psychiatry. 2004;46:269-270
- McNamara JO. Pharmacotherapy of the epilepsies. In: Brunton LL, Laza JS, Parker KL, eds. Goodman and Gilman's The Pharmacological Basis of Therapeutics. 11th ed. New York: McGraw Hills; 2006:515
- Roujeau JC, Kelly JP, Naldi L, Rzany B, Stern RS, Anderson T, et al. Medication use and the risk Stevens - Johnson Syndrome and toxic epidermal necrolysis. N Engl J Med. 1995;333:1600-1607
- Ramya Sree G, Guru SV, Jeeva Kumar ES. Steven Johnson's Syndrome: A Brief Review. International Journal of Pharma Sciences and Research (IJPSR). 2017;8:232-236
- Komulainen T, Lodge T, Hinttala R, Bolszak M, Pietilä M, Koivunen P, et al. Sodium valproate induces mitochondrial respiration dysfunction in HepG2 in vitro cell model. Toxicology. 2015;331:47-56
- Gupta LK, Martin AM, Agarwal N, D'Souza P, Das S, Kumar R, et al. Guidelines for the management of Stevens-Johnson syndrome/toxic epidermal necrolysis: An Indian perspective. Indian J Dermatol Venereol Leprol. 2016;82:603-625
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